Fever occurs when endogenous pyrogens act upon central controls of body temperature to cause an elevation in the level around which body temperature is regulated. The focus of the entire project is upon the events and biochemical processes within the brain which are responsible for the initiation, maintenance and reduction of fever. One line of the continuing research concerns the mechanisms responsible for central inactivation of endogenous pyrogen, a step believed to underlie normal defervescence and defervescence induced by antipyretics. A second line involves tests of proposed central mediators of fever, including prostaglandins of the E series and a protein mediator presumed to originate in the brain. In a third line of research clinical information on febrile patients will be collected and related to the ongoing basic research. The aim is to develop new insights into the central machinisms of fever which will provide a model for understanding cetral fever controls in febrile man.